Patricia Louzon, PharmD, BCPS Clinical Manager, Critical Care and ED … · · 2015-10-20Patricia...

Patricia Louzon, PharmD, BCPS

Clinical Manager, Critical Care and ED Services

Florida Hospital Orlando

Clinical Assistant Professor, University of Florida College of Pharmacy

Discuss evidence based practice for the pharmacologic management of pain, agitation and delirium

78 y/o F admitted from a skilled nursing facility with shortness of breath, cough and fever

PMH: COPD, HTN, CAD, pneumonia

Admitted for suspected pneumonia

Intubated due to worsening respiratory status

Initial pain/agitation/delirium regimen

◦ Midazolam 2mg/hr, titrate to RASS -1 to -2

◦ Morphine 1mg IV q8h PRN pain

Questions:

◦ Is this an appropriate initial regimen for the patient?

Why?

Is there enough information to decide?

What other factors should we look for?

What are some alternatives?

◦ How should her pain and sedation level be assessed?

◦ How should her sedation be titrated?

◦ What other strategies should be employed?

2013 Clinical Practice Guidelines for Adult Patients in the ICU

◦ Pain and Analgesia

◦ Agitation and Sedation

◦ Delirium

Components interrelated

Crit Care Med. 2013 Jan;41(1):263-306.

Delirium

Incidence

◦ ICU patients routinely experience pain

At rest

With routine ICU care

Increased in certain populations (ex post surgical)

Assessment

◦ Behavioral Pain Scale (BPS)

◦ Critical-Care Pain Observation Tool (CPOT)

◦ Vital signs should not be used alone for pain assessment

Crit Care Med. 2013 Jan;41(1):263-306.

Payen et al. Crit Care Med 2001;29(12):2258-63.

Gélinas et al. Am J Crit Care. 2006 Jul;15(4):420-7.

Opiates Onset(IV)

T 1/2 Metabolism Active Metabolites

Inter-mittentDosing

IV Infusion

Rates

Side Effects and Other Information

Fentanyl 1-2 min

2-4 hr Hepatic (CYP3A4/5)

None 25-100mcg IV

q0.5-1 hr

50-700mcg/hr

Less hypotension, accumulation with

hepatic impairment, chest wall rigidity

Hydro-morphone

5-15 min

2-3 hr Hepatic None 0.2-0.6mg IV

q1-2 hr

0.5-3 mg/hr

Accumulation with hepatic/renal

impairment, more potent thanmorphine

Morphine 5-10 min

3-4 hr Hepatic 6- and 3-glucuronide

2-4mg IV

q1-2 hr

2-30mg/hr

Accumulation with hepatic/renal impairment,

Histamine release

Crit Care Med. 2013 Jan;41(1):263-306.

Factors to consider

◦ Age

◦ Renal/hepatic function

◦ Pain level

◦ Is patient opioid tolerant or naïve?

Home pain medications

◦ Interval to schedule

◦ Sources of pain

All available IV opioids, when titrated to similar pain intensity endpoints, are equally effective

Optimal choice of opioid and dosing regimen for individual patient depends on many factors, including the drug’s pharmacokinetic and pharmacodynamic properties

Nonopioid analgesics may be used to decrease the amount of opioids administered

Crit Care Med. 2013 Jan;41(1):263-306.

Delirium

Incidence

◦ Agitation and anxiety occur frequently in critically ill patients

◦ Associated with adverse clinical outcomes

Assessment

◦ Richmond Agitation-Sedation Scale (RASS)

◦ Sedation-Agitation Scale (SAS)

Crit Care Med. 2013 Jan;41(1):263-306.

Sedation is a risk factor

◦ Cognitive impairment

◦ Delirium

◦ Post-ICU post traumatic stress disorder

Midazolam equivalent ≥ 100 mg/day (~4mg/hr)

Mean morphine equivalent ≥ 100mg/day (~4mg/hr)

% of ICU days on opiates is a protective factor!

Bienvenu O.J. Psychological Medicine 2013 (not yet published)

+4 Combative Overtly violent, immediate danger to self and/or staff.

+3 Very Agitated Pulls or removes tube(s) or catheters; aggressive

+2 Agitated Frequent non-purposeful movement, fights ventilator

+1 Restless Anxious, apprehensive, but not aggressive

0 Alert and calm

-1 Drowsy Awakens to voice with eye opening, eye contact (> 10 seconds).

-2 Light sedation Briefly awakens with eye contact to voice (< 10 seconds).

-3 Moderate sedation Movement or eye opening to voice (no eye contact).

-4 Deep sedation No response to voice, but movement or eye opening to physical stimulation

-5 Unarousable No response to voice or physical stimulation.

Ely et al. JAMA. 2003 Jun 11;289(22):2983-91.

Riket et al. Crit Care Med. 1999 Jul;27(7):1325-9.

Propofol(Diprivan®)

Dexmedetomidine(Precedex®)

Midazolam(Versed®)

Lorazepam(Ativan®)

Onset 10-50 sec immediate 1-3 min 5-20 min

Duration 3-10 min 6 min 1-3 hrs, longerwith drips

4-8 hrs, longer with drips

Dosing 5-50 mcg/kg/min 0.1-1 mcg/kg/hr 1-10 mg/hr 1-10 mg/hr

Side effects -Bradycardia-Hypotension-↑ triglycerides-Propofol infusion syndrome (PRIS)-metabolic acidosis, renal failure

-Hypotension-Bradycardia

-Respiratory depression-Delirium

-Respiratory depression-Delirium-Propylene glycol toxicity (vehicle)

Notes - Avoid in heart failure-1.1 calorie/mL due to lipid formula-Avoid long-term use

-Useful for sedative weaning-Can be used in non-intubated-Renewal q5days

- Accumulates in liver failure, duration of action longer

-High risk for delirium-Avoid high-dose, prolonged infusions due to propylene glycol

1) Maintain light sedation levels

2) Daily sedation interruption

3) Light sedation levels PLUS daily interruption

WHICH TO USE???

Lots of evidence!

Ligher sedation arms◦ Shorter duration of mechanical ventilation◦ No increase in clinicically significant physiologic stress (e.g.

myocardial ischemia) ◦ Less (or no change) in PTSD

Crit Care Med 1999; 27: 2609Lancet 2008: 371:126N Engl J Med 2000; 342:1471CHEST 1098; 114:834-6.

Crit Care Med 2007; 35: 365Anesth Analhg 1997; 85:971.Anesthesiology 1997; 86: 785-96Crit Care Med 2003; 830Nurse Crit Care 2007; 12:93.

Intensive Care Med 2006; 32: 93 Crit Care Med 2009; 37: 2527. Am J Respir CCM 2003; 168:1457Nurse Crit Care 2007; 12:93.

◦ Randomized, controlled trial, N=128

◦ Midazolam or propofol and morphine infusions

◦ Interrupted daily until patient responded or became agitated

◦ Restarted at HALF the previous rate if needed

◦ Intervention group had

Shorter duration of mechanical ventilation (4.9 vs 7.3, p=0.004)

Shorter length of stay in ICU (6.4 vs 9.9 days, p=0.02)

No difference in overall length of hospitalization

No difference in complications (self extubation)

Kress et al. N Engl J Med. 2000;342:1471-7.

Randomized, controlled trial, N=430

Protocolized sedation titrated to light sedation vs protocolizedwith daily interruption

If indicated, resumed at HALF the previous rate

◦ No differences

Duration of mechanical ventilation (both 7 days)

Length of stay in ICU (both 10 days)

Overall length of hospitalization (both 20 days)

◦ Interpretation: Addition of daily interruption did not change outcomes

Mehta et al. JAMA. 2012;308 (19):E1-E8.

Maintain light levels of sedation (RASS -1 to -2) unless there is a contraindication

Use EITHER light level of sedation or daily interruption

Nonbenzodiazepine sedatives (propofol or dexmedetomidine) preferred in mechanically ventilated patients

◦ Intermittent pushes alternative strategy to continuous sedation

Choice should be driven by:

1. Specific indications and sedation goals for each patient

2. The clinical pharmacology of the drug

3. Overall costs

Crit Care Med. 2013 Jan;41(1):263-306.

Some patients need deeper sedation!◦ Facilitate mechanical ventilation

Poor oxygenation

Aggressive ventilator settings

Oscillator

◦ Neuromuscular blockers

◦ High risk of self extubation or self harm

◦ History of drug and ethanol abuse

Delirium

Cardinal features◦ A disturbed level of consciousness (i.e., a reduced clarity of

awareness of the environment), with a reduced ability to focus, sustain, or shift attention

◦ Either a change in cognition (i.e., memory deficit, disorientation, language disturbance), or the development of a perceptual disturbance (i.e., hallucinations, delusions)

Subtypes◦ Hyperactive (agitated)◦ Hypoactive (calm or lethargic)

Assessment◦ CAM-ICU or ICDSC

American College of Critical Care Medicine. Crit Care Med. 2013 Jan;41(1):263-306.

Four baseline risk factors positively and significantly associated with the development of delirium in the ICU:

1. Preexisting dementia

2. History of hypertension

3. Alcoholism

4. High severity of illness at admission

Independent risk factors:

◦ Coma

◦ Benzodiazepine use


Varying study findings

Increased development of delirium 1-2

◦ Lorazepam shown to be an independent risk factor 2

Associated with longer delirium duration3

~20% less delirium in a population treated with dexmedetomidine than benzodiazepines in 2 studies 4,5

Other studies showed no relationship 6-8

1. Pandharipande P, et al. J Trauma 2008; 65:34–41 .2. Pandharipande P, et al. Anesthesiology 2006; 104:21–26. 3. Pisani et al. Crit Care Med 2209;37:1-7.4. Riker R et al. JAMA 2009; 301:489–499.5. Pandharipande P, et al. Crit Care 2010; 14:R38.6. Ouimet S. Intensive Care Med 2007; 33:66–73 .7. Lin S et al. J Crit Care 2008; 23: 372–379 .8. Van Rompeay. Crit Care 2009; 13:R77.

Use of different benzodiazepines◦ Midazolam vs. lorazepam

Studies not powered as primary analysis

Different patient populations

General consensus:◦ Potential association

Do any meds need to be

stopped or lowered?

• Especially consider sedatives

• Is patient on minimal amount necessary? – Daily sedation cessation– Targeted sedation plan

• Do sedatives need to be changed?

Toxic Situations• CHF, shock, dehydration• Deliriogenic meds (tight titration)• New organ failure (liver/kidney)

Hypoxemia

Infection/sepsis (nosocomial)

Immobilization

Nonpharm interventions• Hearing aids, glasses, reorient,

sleep protocols, music, noise control, ambulation

K+ or electrolyte problems

Devlin, J.

Haloperidol

(Haldol®)

Quetiapine

(Seroquel®)

Risperidone

(Risperdal®)

Olanzapine

(Zyprexa®)

Ziprasidone

(Geodon®)

Peak Plasma

Time

2-6 hr (PO)

10-20 mins

(IM)

1.5 hr (IR)

6 hr (XR)

1 hr 6 hr (PO)

15-45 mins (short-

acting IM)

7 days (ER- IM)

6-8 hr (PO)

≤ 60 mins (IM)

Half Life 18 hr

3 weeks

(decanoate)

6 hr (IR)

7 hr (XR)

20 hr (PO)

3-6 days (IM)

21-54 hr (IR)

30 days (ER Injection)

7 hr (PO)

2-5 hr (IM)

Dosing 1-5 mg q4-6h 50 mg PO BID 1 mg PO BID 2.5 - 5 mg PO Qday 10 mg IM q2h or 20

mg q4h

Side effects:

QT

prolongation

IV/high doses-

high

PO-Low

Low-to-

Moderate

Low Low Moderate

Anti-

cholinergic

low Low

Dry mouth

rare low rare

Sedation low moderate low moderate low

EPS highest rare moderate low low

Weight gain low moderate moderate highest rare

Notes - Can dose

based on 25%

of bolus doses

required

-Metabolic

changes

-Dyslipidemia

Hyperglycemia

-Can contribute to

delirium

-Renal/hepatic

dose adjustments

-Parkinsonism

-Metabolic changes

- Dyslipidemia

- Hyperglycemia

-IM x 3 days only

-Use with caution in

renal/hepatic

- Max dose

40mg/day

Prevention◦ Perform early mobilization◦ For patients at risk, infusions of dexmedetomidine rather

than benzodiazepines may be associated with lower prevalence No recommendations for use

◦ No recommendation for using a pharmacologic delirium prevention protocol

Treatment◦ No published evidence that treatment with haloperidol

reduces duration of delirium in ICU patients◦ Atypical antipsychotics may reduce the duration of delirium


Delirium

Early mobilization

Promoting sleep by optimizing patients’ environments

Provider education

Use of protocols and order forms

Quality ICU rounds checklists to facilitate the use of pain, agitation, and delirium guidelines or protocols◦ Aim for a light target level of sedation in mechanically

ventilated patients

◦ Analgesia-first sedation use


Implement CAM-ICU screening twice daily

Change to CPOT pain assessment

Pharmacy and interdisciplinary involvement

ABCDE Bundle Rounds

PAD order set trial

Education to RN’s and pharmacy by MD and pharmacist

◦ Daily energizers

◦ Staff meetings

◦ One on one with each included patient

◦ One on one to day and night shift

◦ During interdisciplinary rounds

Daily screening (weekday) of 40 MICU/CCU patients by MD and pharmacist for order set use

Paper orders scanned to pharmacy

Edits to order set periodically based on nursing and physician feedback

Louzon et al. Critical Care Medicine 2013;41(12)suppl.

Retrospective case control study

Primary outcome endpoints:◦ Time on continuous sedation (hours)

Secondary outcome endpoints:◦ Total sedation usage (measured as number of sedative drips

removed from automated dispensing cabinet for patient)

◦ ICU length of stay

◦ Ventilator length of stay (hours)

◦ Re-intubation rates (yes/no)


Inclusion◦ Order set utilized (study group) between October 1, 2012 and

March 15, 2013 OR

◦ Continuous infusion midazolam and fentanyl for > 24 hours in 5800 unit


Exclusion Criteria◦ Age <18

◦ Prisoners

◦ Palliative Care/ terminal condition (cancer, end stage heart disease)

◦ Receiving neuromuscular blockers at time sedation

◦ Chronic respiratory failure prior to admission

◦ Continuous sedation used for < 24 hours


• Similar baseline characteristics

Age

(mean)

History

Etoh/drug

use/psych/

dementia

n (%)

FiO2

(mean)

PEEP

(mean)

On one

pressor

PRN

sedation

used prior

to starting

pilot

Control

n=3556.5 6 (17) 45 6.2 16 (46) 22 (63)

Intervention

n=3568.4 7 (20) 40 5.6 12 (34) 14 (40)

p value 0.002 0.758 0.063 0.120 0.329 0.056


Rass ≥+1

24hr prior

to pilot(mean)

RASS

≥+1 24 hr

post pilot(mean)

Hr until

fentanyl

off (median)

Hr until

Versed

off (mean)

Hr

Precedex

used (median)

# of PRN

fentanyl

doses

given(mean)

# of PRN

Versed

doses

given(mean)

0.8 2 9 3.6 70 2.8 3.7

• ~1 greater RASS of +1/24 hrs than prior to pilot• Potential underutilization of PRN doses of and versed


• 100 Less hours on sedation• 15 Less total sedation drips dispensed• 4.6 Less benzodiazepine drips dispensed• All p values significant

Hrs on

sedation(mean)

Total # drips

dispensed(mean)

# Benzo drips

dispensed(mean)

Control

n=35252.2 27.6 7.3

Intervention

n=35150.3 12.6 2.7

p value 0.0025 <0.001 0.0029


ICU LOS (mean days)

Vent LOS (median days)

Reintubatedn (%)

Mortalityn (%)

Controln=35

16.5 8.56 5 (14) 9 (26)

Interventionn=35

11.5 7.38 3 (9) 8 (23)

p value 0.011 0.07 0.452 0.78

•ICU LOS- 5 days shorter•Vent LOS- 1.18 days shorter•Similar reintubation rates and mortality


Sedation use decreased

Time on continuous sedation decreased

Decrease in ICU LOS


Single way to order sedation regimens

Components:◦ Target RASS -1 to -2◦ Sedation vacation◦ Pain first!◦ Sedation duration expected <72 hours

Non-benzodiazepine strategies◦ Sedation duration expected >72 hours

Consider non-benzodiazepines

Benzodiazepine intermittent dosing preferred

Midazolam preferred to lorazepam

Continuous infusions for select patients only

Integrated Approach to

PADMD Champion

RN Champion

RT Champion

PharmacyChampion

PhysicalTherapy

Champion

HospitalAdministrators

Family

Patient

Courtesy J Barr, MD

Keys to Success

4 E’s◦ Engage

◦ Educate

◦ Execute

◦ Evaluate

Johns Hopkins Critical Care Rehab conference, 2013

Engage/ stimulate interest!

◦ Nurse educator

◦ Physician champions

◦ Grand rounds and faculty meetings

Educate

◦ New sedation protocol, RASS, CAM-ICU

◦ Nursing- lectures, one-on-one, case studies, quiz

◦ Physicians- pocket card

Execute

◦ New sedation protocol

◦ Nurse report Cam-ICU, RASS goal, and RASS scores at rounds

◦ Move to CPOT pain assessment

Evaluate

◦ Monthly barrier review by team

◦ MICU pharmacist feedback at rounds (protocol adherence, delirium management)

◦ Audit RASS and CAM-ICU documentation

78 y/o F admitted from a skilled nursing facility with shortness of breath, cough and fever

PMH: COPD, HTN, CAD, pneumonia

Admitted for suspected pneumonia

Intubated due to worsening respiratory status

Initial pain/agitation/delirium regimen◦ Midazolam 2mg/hr, titrate to RASS -1 to -2

◦ Morphine 1mg IV q8h PRN pain

Questions:

◦ Is this an appropriate initial regimen for the patient?

Why?

What are some alternatives?

◦ How should her pain and sedation level be assessed?

◦ How should her sedation be titrated?

◦ What other strategies should be employed?

Patricia Louzon, PharmD, BCPS

Clinical Manager, Critical Care and ED Services

Florida Hospital Orlando

Clinical Assistant Professor, University of Florida College of Pharmacy

Patricia Louzon, PharmD, BCPS Clinical Manager, Critical Care and ED … · · 2015-10-20Patricia...

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